Study of KITE-197 in Participants With Relapsed or Refractory Large B-cell Lymphoma

A Phase 1 Open-label, Single Arm, Multicenter Study Evaluating the Safety and Efficacy of KITE-197 in Subjects With Relapsed or Refractory Large B-cell Lymphoma

This study will have two Phases: Phase 1a and Phase 1b. The goal of Phase 1a of this clinical study is to learn more about the safety, tolerability and dosing of study drug KITE-197, in participants with relapsed or refractory large B-cell lymphoma (r/rLBCL). The goal of Phase 1b of this clinical study is learn about the effectiveness of the recommended dose of KITE-197 in participants with r/r LBCL.

The primary objectives of this study are:

Phase 1a: To evaluate the safety of KITE-197 in participants with r/r LBCL and determine the target dose level for Phase 1b.

Phase 1b: To evaluate the efficacy of KITE-197 in participants with r/r LBCL as measured by the complete remission (CR) rate.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Large B-cell Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: KITE-197

Detailed Description

Participants will be followed for approximately 6 months after the infusion of KITE-197 before transitioning to a separate Kite long-term follow-up study KT-US-982-5968, in which they will be followed for the remainder of the 15-year follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Royal Brisbane and Women's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Canada
  • Edmonton, Canada, T6G 1Z2
    • Cross Cancer Institute
  • Halifax, Canada, B3H 2Y9
    • QEII Health Sciences Centre
  • Montreal, Canada, H3T 1E2
    • Jewish General Hospital
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
  • Texas
    • Austin, Texas, United States, 78704
      • St. David's South Austin Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Relapsed or Refractory Large B-cell Lymphoma
• At least 1 measurable lesion
• Adequate organ and bone marrow function

Key Exclusion Criteria:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 2 years
• History of Richter's transformation of chronic leukemic lymphoma
• History of allogenic stem cell transplant (SCT)
• Autologous SCT within 6 weeks of planned KITE-197 infusion
• Prior CD19 targeted antibody, such as tafasitamab and loncastuximab with the exception of individuals who have previously achieved an objective response to such therapy and their tumor expresses CD19 by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (IHC) at the time of screening. Individuals who meet these criteria may be eligible
• Prior treatment with bendamustine within 6 months of enrollment
• Prior CAR therapy or other genetically modified cell therapy
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
• History of HIV infection or acute or chronic active hepatitis B or C infection
• History or presence of a clinically significant central nervous system (CNS) disorder Note: Prior or active CNS involvement by lymphoma is not an exclusion criterion.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months before enrollment
• Presence of primary immunodeficiency
• History of autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
• History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism within 3 months before enrollment. Catheter induced DVT which has been treated for at least 6 weeks prior to enrollment is permitted
• Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: KITE-197; Phase 1a (Dose Escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-197 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-197. Phase 1b (Dose Expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-197 CAR-transduced autologous T cells at 1 or more dose-level deemed to be tolerable.

Drug: Cyclophosphamide; Lymphodepleting chemotherapy administered intravenously; Drug: Fludarabine; Lymphodepleting chemotherapy administered intravenously; Drug: KITE-197; A single infusion of CAR-transduced autologous T cells administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)		First infusion date of KITE-197 up to 28 days
Phase 1b: Complete Remission (CR) Rate	Complete remission rate is defined as the proportion of participants with complete remission, per international working group (IWG) Lugano classification, as assessed by the investigator.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Adverse Events (AEs)		Enrollment up to 24 months plus 30 days
Percentage of Participants Experiencing Serious Adverse Events (SAEs)		Enrollment up to 24 months plus 30 days
Overall Response Rate (ORR)	ORR is defined as the proportion of participants with best objective response of either a CR or a partial response (PR) during the trial prior to any new anti-lymphoma therapy, per the Lugano Classification, as determined by the investigator.	Up to 24 months
Duration of Response (DOR)	DOR is defined as the time from first objective response to disease progression or death from any cause among participants who have achieved CR or PR per the Lugano Classification, as determined by the investigator.	Up to 24 months
Progression-Free Survival (PFS)	PFS is defined as the time from KITE-197 infusion to disease progression per the Lugano Classification, as determined by investigator review or death from any cause.	Up to 24 months
Event Free Survival (EFS)	EFS is defined as the time from KITE-197 infusion to the earliest occurrence of death due to any cause, disease progression/relapse per investigator, or initiation of new anti-lymphoma therapy.	Up to 24 months
Time to Next Treatment (TTNT)	TTNT is defined as time from KITE-197 infusion to the start of subsequent new lymphoma therapy or death from any cause.	Up to 24 months
Overall Survival (OS)	OS is defined as the time from KITE-197 infusion to death from any cause.	Up to 24 months
Number of KITE-197 CAR T Cells in Blood Over Time Post Infusion		Up to 24 months
Proportion of Immune Cell Subsets in KITE-197		Up to 24 months

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: October 6, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Recurrence; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: KT-US-656-0601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No